Real Generics’ Regulatory News Digest For Generics – 20 July 2015

Reflection paper on the use of cocrystals of active substances in medicinal products

EMA has adopted a reflection paper (EMA/CHMP/CVMP/QWP/284008/2015) on cocrystals.

Cocrystals are homogeneous crystalline structures consisting of two or more components in a definite stoichiometric ratio. Cocrystals (which also include solvates) differ from salts in being assembled through weaker interactions than ionic bonds, for example hydrogen bonding.

Cocrystallisation may improve solid state properties such as solubility, hygroscopicity and stability. It may also improve manufacturability through better compaction, flowability, etc. Cocrystallisation is therefore of great interest to the pharmaceutical industry, especially because it may be feasible even in cases where salts cannot be formed.

The reflection paper clarifies that cocrystals are eligible for generic applications (Directive 2001/83/EC Article 10(2)(b)) in exactly the same way as salts. In other words, generic products may contain drug substances in cocrystal form even if the reference product is in a different form. This is because the weak interactions within cocrystals are generally broken when the material dissolves, releasing the same active moiety as the reference product. The need to demonstrate equivalent safety and efficacy remains.

It is also possible to submit a fixed dose combination containing two or more drug substances presented as a cocrystal. This is not regarded as a new active substance unless it exposes the patient to different therapeutic moieties compared to products already authorised.

The overview of comments received on the reflection paper may also be of interest (EMA/CHMP/CVMP/QWP/284007/2015).


EMA Product-Specific Bioequivalence Guidance

EMA has released draft product-specific bioequivalence guidance for consultation, for the following products:

Zonisamide 25 mg, 50 mg and 100 mg hard capsules, and 25 mg, 50 mg, 100 mg and 300mg orodispersible tablets

Sitagliptin 25 mg, 50 mg and 100mg film-coated tablets

Prasugrel 5 mg and 10 mg film-coated tablets

Asenapine 5 mg and 10 mg sublingual tablets

The consultation end date is 1 November 2015.



Real Generics Ltd is a member of the Real Regulatory Group. The partner company, Real Regulatory Ltd, is a consultancy firm specialising in European Regulatory Affairs, Quality Management Systems and Supply Chain Operations Compliance for the pharmaceutical, medical device and aligned industries.

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Photograph: Sugar cane crystals by Cristóbal Alvarado Minic, CC BY 2.0

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